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HLA matching is not considered in recipient selection for lung transplantation. This study retrospectively examined a large cohort of lung transplants from the Organ Procurement and Transplantation Network (OPTN) database to evaluate the effect of HLA matching on survival, bronchiolitis obliterans, and acute rejection. Significantly improved survival was seen in recipients with fewer total HLA and Class I mismatches. Patients with fewer total Class I mismatches had lower incidence of bronchiolitis obliterans syndrome. Increased incidence of acute rejection was associated with Class II mismatches. Total HLA, Class I, and Class II mismatches impacted recipient survival. Although HLA matching in lung transplantation currently faces challenges, understanding the implications of mismatches may eventually lead to improved survival.